A series of consecutive antibiotic trials for suspected sepsis in granulocytopenic cancer patients began in 1969 and continues to the present. Initial evaluations proved the usefulness of carbenicillin and gentamicin and later trials, including a large multi-institutional trial, indicated that carbenicillin (ticarcillin) plus gentamicin had the best efficacy-to-toxicity ratio of the three possible two-drug combinations of carbenicillin (ticarcillin), gentamicin and cephalothin. The following two-drug combinations were therefore evaluated: ticarcillin plus gentamicin, ticarcillin plus amikacin and ticarcillin plus netilmicin. In 183 consecutive patient-trials, the efficacy was high and the toxicity minimal. With the addition of early granulocyte transfusions for poor risk patients, a response rate of over 90% was achieved. A new penicillin derivative, mezlocillin, with exceedingly broad activity was utilized alone in 50 consecutive patients but proved less than satisfactory in the absence of concomitant aminoglycoside therapy. Therefore, ticarcillin plus amikacin became standard therapy to which piperacillin (a new broad spectrum penicillin) plus amikacin and moxalactam (a new broad spectrum cephalosporin) plus amikacin have been compared with excellent results.